Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-20256
Renkema, K Y; Velic, A; Dijkman, H B; Verkaart, S; van der Kemp, A W; Nowik, M; Timmermans, K; Doucet, A; Wagner, C A; Bindels, R J; Hoenderop, J G (2009). The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis. Journal of the American Society of Nephrology (JASN), 20(8):1705-1713.
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Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5(-/-)) mice lack kidney stones despite urinary calcium (Ca(2+)) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms. Exposure of dissected mouse outer medullary collecting ducts to high (5.0 mM) extracellular Ca(2+) stimulated H(+)-ATPase activity. In TRPV5(-/-) mice, activation of the renal Ca(2+)-sensing receptor promoted H(+)-ATPase-mediated H(+) excretion and downregulation of aquaporin 2, leading to urinary acidification and polyuria, respectively. Gene ablation of the collecting duct-specific B1 subunit of H(+)-ATPase in TRPV5(-/-) mice abolished the enhanced urinary acidification, which resulted in severe tubular precipitations of Ca(2+)-phosphate in the renal medulla. In conclusion, activation of Ca(2+)-sensing receptor by increased luminal Ca(2+) leads to urinary acidification and polyuria. These beneficial adaptations facilitate the excretion of large amounts of soluble Ca(2+), which is crucial to prevent the formation of kidney stones.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||18 Aug 2009 13:26|
|Last Modified:||27 Nov 2013 21:08|
|Publisher:||American Society of Nephrology|
|Citations:||Web of Science®. Times cited: 40|
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